Cerebral Aqueduct CSF Stroke Volume Hydrodynamics in Chronic Communicating Hydrocephalus: Exploration of the Initial and Late Phases in an Animal Model

Abstract

INTRODUCTION Early diagnosis of NPH during its initial stages is almost impossible, given the delayed onset of clinical symptoms, making the study and the understanding of the CSF dynamics very challenging in human subjects. In this study, we explore these dynamics in a novel animal model with induced chronic communicating hydrocephalus with the aim to better understand the pathophysiology of NPH to pursue earlier diagnostic tools that will ultimately translate into better treatment outcomes. METHODS Chronic communicating hydrocephalus was induced in 15 adult Sprague-Dawley rats using a technique developed by our group. Kaolin is injected into the subarachnoid space over the cerebral convexities. Additionally, 4 animals were used as controls and 3 as shams with saline injections. PCMRI was performed to calculate the aqueductal stroke volume (ASV) and T2-W images for ventricular size measurements on days 15, 60, 90, and 120 using a Bruker 11.7-TMR. Nonparametric tests were implemented to analyze the ASV and its correlation with the ventricular volumes after the hydrocephalus induction. RESULTS Kaolin-injected (KI) animals showed a significant ventricular enlargement at all time points. A significant difference in ASV was present between KI and controls at all times. There was a significant positive correlation between the ventricular volume expansion and the ASV between 15 and 60 d. CONCLUSION An initial active phase of rapid ventricular enlargement shows a strong correlation between the expansion of the ventricular volume and the increment in ASV during the first 60 d, followed by a second phase with a less ventricular enlargement and heterogeneous behavior in the ASV. Results may suggest an optimal window for CSF diversion treatment. This hypothesis will be explored in the following experiment by shunting groups of animals at all time points. Future studies will include an evaluation of the intracranial pressure and histological/microstructural analysis to better understand the ASV variations after 60 d.